for medical use
active substance: glimepiride;
1 tablet contains glimepiride 2 mg, 3 mg or 4 mg;
excipients (tablets2 mg): lactose monohydrate, sodium starch glycolate, (type A), povidone K 30, microcrystalline cellulose, magnesium stearate, iron oxide yellow (E 172), iron oxide red (E 172);
excipients (tablets3 mg): lactose monohydrate, sodium starch glycolate, (type A), povidone K 30, microcrystalline cellulose, magnesium stearate;
excipients (tablets4 mg): lactose monohydrate, sodium starch glycolate, (type A), povidone K 30, microcrystalline cellulose, magnesium stearate, iron oxide yellow (E 172), iron oxide red (E 172)
Pharmaceutical form. Tablets.
Antidiabetic agents. Oral hypoglycemic agents, except insulin. Sulfonamides, urea derivatives. Code АТС А10В В12.
Insulin-dependent diabetes mellitus type 2, if blood glucose level cannot be adequately controlled only by diet, physical exercises and by decreasing body weight.
Hypersensitivity to glimepiride or any other component of the drug, to sulfonylurea derivatives or other sulfonamides. Insulin-dependent diabetes mellitus type 1, diabetic ketoacidosis, diabetic coma, severe liver or kidneys dysfunctions.
In case of severe liver or kidney dysfunction it is recommended to transfer the patient to insulin treatment.
Administration and dosage.
Successful treatment of diabetes mellitus depends on patient’s adherence to an appropriate diet, regular physical activity and continuous monitoring of glucose levels in blood and urine. Patient’s failure to adhere to the diet is not compensated by taking tablets or insulin. The drug is used in adults. The tablet should be swallowed without chewing, followed by liquid.
The dosage depends on serum and urine glucose levels. Generally, Glimax® is used once daily. It is recommended to use the drug shortly before or with a substantial breakfast or, if breakfast is not taken, shortly before or with the main meal. If you have missed a regular dose, do not increase the next dose.
The initial dose is 1 mg of glimepiride daily. If such dose helps to adequately control the sugar level, it should be used as a supporting dose.
If glycemic control is not optimal, the dose should be gradually increased (with an interval of 1-2 weeks) to 2, 3 or 4 mg of glimepiride daily. If the patient experiences hypoglycemic reaction to 1 mg of Glimax per day, this means that the disease may be controlled only by the diet. The dose of more than 4 mg daily gives better results only in isolated cases. The maximum recommended dose is 6 mg of Glimax daily.
Combination with metformin.
If the maximum daily dose of metformin does not provide a sufficient glycemic control, a concomitant therapy with glimepiride may be started. Adhering to the previous dose of metformin, Glimax therapy should be started with a low dose (1 mg), which may be gradually increased later to maximum daily dose, focusing on the desired level of metabolic control. The combined therapy should be conducted under close medical supervision.
Combination with insulin.
If maximum daily dose of Glimax does not provide adequate glycemic control, if necessary, a concomitant treatment with insulin may be started. Adhering to the previous dose of glimepiride, insulin therapy should be started with the lowest dose, which may be gradually increased later to maximum daily dose, focusing on the desired level of metabolic control. The combined therapy should be conducted under close medical supervision.
Improved controllability of diabetes is accompanied by increased insulin sensitivity, therefore, during the therapy the need for glimepiride may decrease. To avoid hypoglycemia, the dose should be decreased or the therapy should be discontinued. It may be also necessary to revise the dosage if the patient’s body weight or life style has changed, or if there are other factors that increase the risk of hypo- or hyperglycemia.
Transfer from oral hypoglycemic agents to Glimax®.
Usually, it is possible to transfer to Glimax therapy from other oral hypoglycemic agents. During such transfer, the effect and half-life of the previous agent should be taken into account. In some cases, especially if the anti-diabetic drug has long half-life period (such as chlorpropamide), it is recommended to wait several days before starting Glimax. This will help reduce the risk of hypoglycemic reactions due to the additive action of two agents. The recommended initial dose is 1 mg of glimepiride daily. the dose may be gradually increased, taking into account reaction to the drug.
Transfer from insulin to Glimax®.
In exceptional cases, patients with diabetes mellitus type 2 taking insulin may be recommended to transfer to Glimax®. Such transfer should be performed only under close medical supervision.
Blood system: rare – moderate to severe thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, erythropenia, hemolytic anemia and pancytopenia, which usually disappear after stopping of treatment.
Immune system: very rare – allergic vasculitis, hypersensitivity reactions ranging from minor to severe with the development of dyspnea, decreased blood pressure, sometimes shock. Cross allergy to sulfonylurea, sulfonamide or related compounds is possible.
Metabolic disorders: rare – hypoglycemic reactions, which occur mainly at the beginning of treatment, may acquire severe forms and are not always easy to treat (the symptoms of hypoglycemia are given in section “Overdose”). The occurrence of these reactions depends on subjective factors, such as eating habits and dosage.
Eye disorders: due to changes in blood glucose levels, temporary visual impairments may occur, especially at the beginning of treatment.
Digestive tract: very rare – nausea, vomiting, diarrhea, feeling of pressure or abdominal fullness, abdominal pain, which can sometimes lead to discontinuation of therapy.
Hepatobiliary system: increase in liver enzymes may be observed, very rare – abnormal liver function (e.g., cholestasis and jaundice), hepatitis B, which can progress to liver failure.
Skin and subcutaneous tissue: hypersensitivity reactions: itching, rashes and urticaria, very rare – increased sensitivity to light.
Laboratory findings: very rare – reduction of sodium level in blood serum.
An overdose may cause hypoglycemia, which lasts from 12 to 72 hours, and may recur after the first relief. The symptoms may appear within 24 hours after absorption of the drug. Typically, such patients should be in the in-patient department.
Symptoms of hypoglycemia: nausea, vomiting and pain in the stomach, headache, tremor, blurred vision, loss of coordination, drowsiness, sleep disturbances, anxiety, aggressiveness, impaired concentration and reaction rate, depression, disorientation, speech disorders, aphasia, paresis, sensory disturbances, dizziness, helplessness, loss of self-control, delirium, cerebral convulsions, loss of consciousness up to development of coma, shallow respiration and bradycardia. Moreover, such symptoms of reverse adrenergic reaction, as excessive sweating, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmia may be observed. The clinical presentation of severe hypoglycemic attack may resemble a stroke.
Treatment. The treatment first of all consists in prevention of absorption of the drug. For this, induce vomiting, and then during water or lemonade with activated carbon (adsorbent), laxative is indicated. In case of severe overdose, hospitalization to the intensive therapy unit is necessary. Administration of glucose should be started as soon as possible: if necessary, first, a one-time injection of 50 mL of a 50% solution, and then intravenous infusion of 10% solution, with constant control of blood glucose level. The further treatment is symptomatic.
Using during pregnancy or breastfeeding.
The drug is not used during pregnancy. If the patient receiving glimepiride is planning to conceive or is pregnant, she should be transferred to insulin therapy as soon as possible.
As other sulphonylurea derivatives are excreted in breast milk, it is recommended to stop the treatment with glimepiride due to the risk of hypoglycemia in newborn.
The drug is not used.
Peculiarities of use.
An appropriate diet, regular physical exercises and, if necessary, decrease in body weight are as important to achieve the optimal blood sugar level, as regular use of glimepiride. The clinical symptoms of insufficient decrease in blood sugar level (hyperglycemia) are increased frequency of urination, excessive thirst, dry mouth and dry skin.
Glimax® should be taken shortly before or during the meal. If meals are taken at different time each time, or skipped, the drug may cause hypoglycemia. The symptoms may be almost always quickly reduced by taking carbohydrates (sugar) immediately.
Artificial sweeteners have no effect.
On the basis of the experience of using sulphonylurea derivatives it is known that countermeasures may be successful at first, but despite this, the symptoms of hypoglycemia may occur again.
Severe and prolonged hypoglycemia, which may be reduced only temporary using the normal amount of sugar, requires immediate medicinal treatment, and sometimes hospitalization.
The factors that promote the occurrence of hypoglycemia are: unwillingness or (more often in older patients), inability to cooperate with the physician; malnutrition, irregular meals or skipped meals, periods of starvation; changes in diet; imbalance between physical load and carbohydrate intake; alcohol consumption, especially in conjunction with missed meals; mild renal and liver dysfunction; overdose of Glimax®; certain uncompensated endocrine disorders that affect the metabolism of carbohydrates, or counter regulation of hypoglycemia (e.g., thyroid dysfunction, insufficiency of the anterior pituitary or adrenal gland cortex), concomitant use of certain drugs.
In course of treatment with Glimax, glucose level in blood and urine should be constantly monitored.
Besides, it is recommended to control the amount of glycosylated hemoglobin.
When using the drug, regular monitoring of liver function and blood count (especially the number of leukocytes and platelets) is necessary.
In stressful situations (e.g., accidents, urgent operations, infections that are accompanied by fever), temporary transfer of patient back to insulin is recommended.
here are no data regarding the use of Glimax in patients with severe hepatic impairment or those who are recommended dialysis. Patients with severe renal or hepatic insufficiency should be transferred to insulin.
It should be taken into account that the symptoms of hypoglycemia may be hidden or absent in elderly patients with vegetative neuropathy, or those who receive concomitant treatment with β-adrenergic blockers, reserpine, clonidine, guanethidine or other sympatholytic agents. If the effect is insufficient or reduced, the combination with metformin or insulin is recommended in case of prolonged therapy.
In case of compensation of diabetes mellitus, insulin sensitivity increases, due to which in course of treatment the need for the drug may decrease. The dose should also be adjusted in case of changes in the patient’s body weight or life style, of in case of emergence of other factors that induce hypo- or hyperglycemia.
The drug should not be administered in patients with rare hereditary galactose intolerance, lactase deficiency or malabsorption of glucose-galactose.
Effect on reaction rate when driving motor transport or operating other mechanisms.
The drug may impair such functions as concentration, reaction rate, which is the result of hypo or hyperglycemia, as well as the consequence of vision disorders. This should be taken into account by patients performing potentially hazardous activities, which require increased attention and high psychomotor reaction rate.
Drug interactions and other types of interactions.
Coadministration of Glimax with certain drugs may reduce or induce hypoglycemic effect of glimepiride. Therefore, other drugs should be taken only with the consent (or by prescription) of physician. Glimepiride is metabolized by cytochrome Р450 (CYP2C9). It is known that due to coadministration of inducers (e.g., rifampicin) or inhibitors (e.g., fluconazole) of CYP2C9 this metabolism may vary. Fluconazole, one of the strongest CYP2C9 inhibitors, almost doubles AUC of glimepiride.
Increase the effect of glimepiride in coadministration: phenylbutazone, azapropazone, oxyphenbutazone, sulfinpyrazone, insulin and oral antidiabetic drugs, certain sulphonamides, metformin, tetracyclines, salicylates and p-amino-salicylic acid, MAO-inhibitors, anabolic steroids and male sex hormones, quinolone antibiotics, chloramphenicol, probenecid, coumarin anticoagulants, miconazole, fenfluramine, pentoxifylline (high dose parenteral), fibrates, tritoqualine, ACE inhibitors fluconazole, fluoxetine, allopurinol, sympatholytics, cyclophosphamide, isophosphamide, throphosphamide, disopyramide, phenyramidol, guanethidine.
Decrease hypoglycemic effect of glimepiride in coadministration: estrogens and progestogens, saluretics, thiazide diuretics, thyroid hormones and thyroid stimulating agents, corticosteroids and glucocorticosteroids, phenothiazine derivatives, chlorpromazine, epinephrine and other sympathomimetics, nicotinic acid (high doses) and its derivatives, glucagon, laxatives (long term use), phenytoin, diazoxide, barbiturates, rifampicin, acetazolamide.
Н2-receptor antagonists, -blockers, clonidine and reserpine may either potentiate or weaken hypoglycemic effect. Under the influence of sympatholytics, such as -blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter regulation of hypoglycemia may reduce or disappear. Alcohol intake may potentiate or weaken the hypoglycemic effect of glimepiride in an unpredictable way.
Glimepiride may either potentiate or weaken the effect of coumarin derivatives.
Pharmacodynamics. Glimepiride is an oral hypoglycemic agent, sulphonylurea derivative. It stimulates insulin secretion by pancreatic β-cells, increases insulin release, increases peripheral insulin sensitivity. Maximum effect is achieved after 2-3 hours and lasts more than 24 hours.
Pharmacokinetics. When administered orally, glimepiride is completely absorbed regardless of meal. Maximum serum concentration is reached 2.5 hours after the intake. The volume of distribution is low (about 8.8 liters), clearance is about 48 mL/min, binding to plasma proteins is about 99%. The half-life is about 5-8 hours. After taking high doses of the drug, the half-life period increases.
Glimepiride is metabolized in the liver to hydroxyl derivatives, which are excreted in urine (about 58% of single dose of the drug) and in feces (35-40%).
There has been no significant difference found in pharmacokinetics when using a single dose of the drug or using it during several days one time daily. The drug is not accumulated. Pharmacokinetic parameters in patients of various age and sex are alike.
There is a tendency for glimepiride clearance to increaseand for its average serum concentrations to decrease in patients with renal impairment.
General physical and chemical properties:
tablets2 mg: light-yellow round flat tablets with a score line on one side and smooth on the other;
tablets3 mg: white, round flat tablets with a score line on one side and smooth on the other;
tablets4 mg: light-pink, round flat tablets with a score line on one side and smooth on the other.
Shelf-life. 3 years.
Store at the temperature not more than 25 ℃ in a dry place protected from sunlight.
Keep out of reach of children.
10 tablets are in a blister; 3 or 6, or 10 blisters are in a carton.
Category of supply.On prescription.
“Kusum Pharm” LTD.
Ukraine, 40030, Sumy, 54, Skriabina St.
Date of last revision.